RIC1

Chr 9

RIC1 partner of RAB6A GEF complex

Also known as: CATIFA, CIP150, KIAA1432, bA207C16.1

NCBI Gene: 57589 ENSG00000107036 UniProt: Q4ADV7

The RIC1 protein forms a guanine nucleotide exchange factor complex that activates RAB6A to facilitate endosome-to-Golgi vesicle fusion and is required for procollagen transport, secretion, and craniofacial skeletal development. Biallelic mutations cause CATIFA syndrome, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.398), indicating that complete loss of function is likely pathogenic.

ResearchSummary from RefSeq, OMIM, UniProt

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.40

Clinical Summary— RIC1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 191 VUS of 262 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.001

Z-score 5.85

OE 0.28 (0.20–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.93–1.05)

747 obs / 752.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.20–0.40)

0≤0.351.4

Missense OE?0.99 (0.93–1.05)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 21 / 76.1Missense obs/exp: 747 / 752.7Syn Z: -5.29

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedRIC1-related syndromic congenital cataractOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4090th %ile

GOF

0.3491th %ile

LOF

0.66top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

262 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS191

Likely Benign28

Benign8

Conflicting2

Likely Pathogenic

191

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	3	185	2	1	191
Likely Benign	0	13	2	13	28
Benign	0	1	3	4	8
Conflicting	—				2
Total	3	200	7	18	230

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

162 pathogenic / likely-pathogenic (of 171) ClinVar copy-number / structural variants overlap RIC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →